Penicillin salt of alpha-phenyl-beta-dibenzylaminoethanol



Patented June 29, 1954 PENICILLIN SALT OF a-PHENYL-fl- DIBENZYLAMINOETHANOL Frank H. Buckwalter, De Witt, and-Alphonse P. Granatek, Syracuse, N. Y., assignors to Bristol Laboratories Inc., Syracuse, N. Y., a corporation of New York No Drawing. Application March 13, 1952,

4 Claims. 1

The present invention relates to a new, nontoxic, water-insoluble, amine salt of penicillin, more particularly a penicillin salt of a-phenyl-B- dibenzylaminoethanol, which is capable of exerting a repository antibiotic action and for'use as a supplement in animal and poultry feeds.

The new penicillin salt of the present invention has the following formula Alpha-phenyl-beta-dibenzylaminoethanol Following Emerson (J. Amer. Chem. Soc. 67, 516 (1945)), a mixture of 60 g. (0.5 mole) of styrene oxide and 131 g. (0.67 mole) of dibenzylamine were heated at 100 C. for two hours, allowed to stand at room temperature for 64 hours and then heated at 100 C. for five hours. Upon distillation, the a-phenyl-B-dibenzylaminoethanol was collected at 210215 C./1 mm. The hydrochloride is precipitated by passing hydrogen chloride into a cold, ethereal solution of this free base.

EXAMPLEII Penicillin G salt of alpha-phenyl-beta-dibenzylaminoethanol 0.64 g. of a-phenyl-;8-dibenzylaminoethanol hydrochloride in 10 cc. of water is added to 0.66 g. of sodium penicillin G in cc. of water. Upon scratching and cooling, the crystalline penicillin G salt of a-phenyl-fi-dibenzylaminoethano1 precipitates and is collected by filtration. This salt has a potency of about 900 units/mgm. and is soluble in water at room temperature to the extent of about 100 units/cc.

EXAMPLE HI Potassium penicillin G (18.6 g.; 0.05 mole) is shaken with 75 m1. of 8.5% phosphoric acid and Serial No. 276,455

150 ml. of ether in the cold until two clear layers result. The aqueous layer is withdrawn and discarded. The ether solution is filtered and then added all at once to a cold solution of 0.04 mole (12.7 g.) of a-phenyl-B-dibenzylaminoethanol in 50 ml. of ether. Crystalline penicillin G salt of a-phenyl ,6 dibenzylaminoethanol precipitates and is collected by filtration.

While the present invention has been described with particular reference to the oc-DhGIlYl-B-dibenzylaminoethanol salt of penicillin G it will be understood that the a-phenyl-fl-dibenzylamino ethanol salts of other *penicillins are also included within the scope of this invention. For instance, penicillins such as the penicillins G, F, X, dihydro F, O and K and mixtures of two or more such penicillins, particularlysuch mixtures containing at least of penicillin G, are included within the scope of this invention.

It will be understood that the reaction can be carried out in water-immiscible organic solvents other than ether. Examples of such solvents are butanol, amyl acetate, methyl amyl acetate, isopropyl ether, mesityl oxide, methyl isobutyl ketone, methylene dichloride, ethylene dichloride and chloroform. Recovery of the product may be increased by evaporating the solvent in vacuo at low temperatures.

It will be understood also that the ethereal solution of the free base may be prepared in ether by the use of caustic to liberate the free amine from an organic-solvent soluble or water soluble salt such as the hydrochloride, phosphate, nitrate, hydrobromide, sulfate, citrate, acetate, and tartrate.

It will .be understood that, without departing from the spirit of the invention or the scope of the claims, various modifications may be made in the specific expedients described as these are illustrative only.

We claim:

1. A salt of penicillin and a-phenyl-fi-dibenzylaminoethanol. I

2. A salt of penicillin G and a-phenyl-fl-dibenzylaminoethanol.

3. A salt of penicillin O and a-DhGl'lYl-fi-dibenzylaminoethanol.

4. A salt of penicillin dihydro F and (vi-phenylc-dibenzylaminoethanol.

References Cited in the file of this patent UNITED STATES PATENTS 

1. A SALT OF PENICILLIN AND A-PHENYL-B-DIBENZYLAMINOETHANOL. 